The descriptions of the pathology of virus infections of the CNS are very thorough, but little is known about the interactions which take place between the infecting virus and the neural host cell. The purpose of this research program is to do the molecular investigation of such an infection studying as a model system the human papovavirus, JCV, as it establishes a chronic infection of oligodendroglial cells in the brains of humans described as a progressive multifocal leucoencephalopathy (PML). As a member of the pap vavirus family, JCV also has oncogenic potential, being able to induce glioblastomas in both owl and squirrel monkeys. What we have found is that the JCV genome integrates its DNA into the chromosomes of primate glioblastomas in one to several copies and that the integration occurs in discrete retions of the host chromsome perhaps indicating that the development of these types of tumors are cell clonal in nature and not a multicellular participation. We have further determined that the JCV genomel produces a gene product responsible for these neoplastic changes, a T protein of 94K daltons. We have detected this protein using a mouse monoclonal antibody to the SV40 T protein which specifically identifies the JC T protein. As a consequence of its expression, the glioblastoma cells secrete plasminogen activator (PA) into their medium unlike normal cells which retain much of their PA inside the cells. We have also determined that cytoskeletal changes if actin fiber disorganization take place as a result of JCV gene expression. To study the control of these genes in more depth, we have cloned them into plasmid vectors using recombinant DNA methods and introduced them into glial cells and other cell types. The 94K, T proteins is synthesized in glial cells but a smaller 20K, t protein apparently is not. More importantly a host protein, p53K, which appears to be a regulatory protein both for the cell and viral proteins, does not seem to interact with the JC T proteins but does so with other papovavirus T proteins. We have also made this observation in JC induced glioblastoma cells as well as permissive glial cells.